THE ROLE OF LIPOPROTEIN-LIPASE AND APOPROTEIN-E IN THE RECOGNITION OFCHYLOMICRONS AND CHYLOMICRON REMNANTS BY CULTURED ISOLATED MOUSE HEPATOCYTES

Lipoprotein lipase (LPL) has been proposed to play a role in the uptak e of chylomicron remnants by hepatocytes by mediating the binding of t hese lipoproteins to cell-surface glycosaminoglycans and to the low-de nsity-lipoprotein receptor-related protein (LRP). This proposal is bas ed on studies that examined the binding of chylomicrons to HepGZ cells , fibroblasts and Chinese hamster ovary cells in culture, in the prese nce of large amounts of LPL [Beisiegel (1995) Curr. Opin. Lipidol. 6, 117-122]. We have investigated whether LPL attached to the surface of chylomicrons enhances the binding and uptake of these lipoproteins to isolated hepatocytes maintained in culture. Bovine milk LPL was bound to mouse chylomicrons, double-labelled in vivo with [H-3]retinol (in r etinyl esters) and with [C-14]palmitic acid (in triacylglycerols), col lected from the mesenteric lymph of normal mice and from mice lacking the apoprotein E (apo E) gene, Normal chylomicrons (containing apo E) and apo E-free chylomicrons, with or without bound LPL, were incubated with cultured hepatocytes isolated from mice lacking the apo E gene, At 0 degrees C LPL did not enhance the binding of the normal or apo E- free chylomicrons by the hepatocytes. When incubations were performed at 37 degrees C the triacylglycerols of normal and apo E-free chylomic rons were hydrolysed by LPL and there was a significant uptake of [C-1 4]fatty acids and [H-3]retinol by the hepatocytes. The addition of hep arin or lactoferrin, a known inhibitor of hepatic uptake of chylomicro n remnants, to the incubation medium inhibited the uptake of[3H]retino l, present in the lipoprotein core, but not the uptake of the [C-14]fa tty acids. We conclude that: (1) LPL attached to chylomicrons in amoun ts sufficient to effectively hydrolyse their core triacylglycerols doe s not enhance the binding of these lipoproteins to the surface of isol ated hepatocytes; (2) the recognition and uptake of chylomicrons by he patocytes requires that these lipoproteins be first hydrolysed by LPL; and (3) the uptake of lipolysed chylomicrons (remnants) by hepatocyte s does not require the mediation of apo E.